To investigate the bioequivalence of the final tablet formulation of eslicarbazepine acetate (ESL) and the tablet formulation used in pivotal clinical studies.Methods: Single centre (Algorithme Pharma, Quebec, Canada) study consisting of three single-dose, randomized, two-way crossover sub-studies in healthy subjects.In each sub-study (n=20), the bioavailability of BIA 2-005 (ESL active metabolite) following a given ESL tablet strength (400 mg, 600 mg or 800 mg) of the final formulation (Test) was compared with the corresponding tablet strength of the research formulation (Reference), under fasting conditions. The statistical method for testing bioequivalence was based upon the 90% confidence interval (90%CI) for the Test/Reference geometric mean ratio (GMR) for C max , AUC 0-t and AUC 0-∞ . Bioequivalence was to be assumed when the 90%CI fell within the recommended acceptance interval 80.00%; 125.00%. Results:The Test/Reference GMR and 90%CI for BIA 2-005 were as follows: 400 mg tablets -105.37% (99.57%; 111.52%), 102.83 (99.19%; 106.61%) and 102.83% (99.13%; 106.66%) for C max , AUC 0-t and AUC 0-∞ , respectively; 600 mg tablets -102.65% (97.27%; 108.33%), 102.40% (99.00%; 105.93%) and 102.38% (98.97%; 105.90%) for C max , AUC 0-t and AUC 0-∞ , respectively; 800 mg tablets -104.16% (95.44%; 113.67%), 100.34% (97.85%; 102.90%) and 99.88% (97.65%; 102.16%) for C max , AUC 0-t and AUC 0-∞ , respectively. Conclusion:The 90%CI of all pharmacokinetic parameters of interest (C max , AUC 0-t , and AUC 0-∞ ) fell within the acceptance range of 80.00%; 125.00%. Therefore, bioequivalence of the final tablet formulation and the tablet formulation used in the pivotal clinical trials of ESL has been demonstrated.
The bioequivalence criteria between the ESL 400 mg and 800 mg tablets were met and dosage form proportionality was demonstrated. The presence of food had no influence on ESL pharmacokinetics, indicating that ESL can be administered without regard to meals with no significant effects on drug disposition or extent of systemic exposure.
The pharmacokinetic profiles of eslicarbazepine acetate oral 50 mg/mL suspension, 200mg tablet and 800mg tablet formulations were essentially similar, and the formulations can be considered bioequivalent.
Purpose To compare the bioavailability (BA) and pharmacokinetic (PK) properties and to demonstrate the bioequivalence (BE) between two active product ingredient (API) sources of eslicarbazepine acetate (ESL) in healthy volunteers. Design, subjects and methods Forty healthy male and female subjects aged 18-40 years were randomized to treatment with 400 or 800 mg ESL marketed (MF) formulation [current active pharmaceutical ingredient (API) source] and 400 or 800 mg ESL to-be-marketed (TBM) formulation (new API source) under a gender-balanced, two-period, two-sequence crossover open-label study design. Subjects were assigned to receive either 400 or 800 mg ESL dose strengths, and each was randomly administered on two occasions-either a single oral tablet of MF or a single oral tablet of TBM-separated by a washout period of at least 7 days. Formulations were to be considered bioequivalent if, for both 400 or 800 mg ESL dosage strengths, the test (TBM)/reference (MF) geometric mean ratios (GMR) and 90 % confidence intervals (90 % CI) of the area under the plasma concentration-time curve (AUC) and peak plasma concentration (C max ) were within the predetermined range of 80-125 %. Results Test/reference GMR (90 % CI) for the C max and AUC was respectively 100 % (94-109 %) and 96 % (94-98 %) following 400 mg ESL and 100 % (95-105 %) and 100 % (97-103 %) following 800 mg ESL. Conclusion Oral tablet formulations of either 400 or 800 mg ESL from the new API source were found to be bioequivalent to the corresponding marketed Zebinix Ò formulation according to the regulatory definition of bioequivalence.
The antioxidant, photoprotective and antinociceptive Marcetia macrophylla active extract was investigated as an active ingredient in a sunscreen cream formulation. Thus, the M. macrophylla extract showed IC50 of 3.43 mg/ml of the antioxidant (DPPH∙ scavenging test) and Sun Protection Factor of 20.25 (SPF/UV-B, at 250 µg/ml) and UV-A of 78.09% (photobleaching trans-resveratrol test). The antinociceptive activity was superior to all standards tested using the in vivo acetic acid-induced writhing test (99.14% at the dose of 200 mg/kg) and the high-performance liquid chromatography coupled with diode array detector and mass spectroscopy multi-stage (HPLC-DAD-MS/MS) enabled the structural characterization of the quercetin-3-O-hexoside, quercetin-3-O-pentoside and quercetin-3-O-desoxihexoside. The pharmaceutical formulation containing the Marcetia macrophylla crude active extract was prepared and the physicochemical tests (organoleptic characteristics, pH analysis and centrifugation), the in vitro UVB (sun protection factor, SPF) and UVA (β-carotene) using the spectroscopic method were investigated. The formulation showed satisfactory results concerning the physicochemical parameters evaluated and active against the UV test. Thus, M. macrophylla showed biological activities with potential use in pharmaceutical preparations.
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